Parathyroid hormone (PTH) has been implicated as a systemic factor that increases alveolar bone resorption in periodontal disease. Recent radioimmunoassay evidence indicates that there are multiple metabolites of PTH in the circulation, some of which may possess biological activity related to this disease, thus indicating that a more detailed investigation into PTH peripheral metabolism is needed. Our development of a simple electrolytic iodination procedure for the production of 125I-tryosine-labeled PTH possessing apparently full biological activity has promoted us to start on an investigation of the metabolism of PTH. A series of preliminary experiments indicated that 125I-PTH administered to rats was deposited very rapidly in three organ systems only: bone, kidney and liver. As indicated by increasing solubility in trichloracetic acid, the hormone seemed to be rapidly metabolized at the sites of deposition. Based on this information, quantitative extraction and gel filtration procedures were developed for the characterization of metabolites. It was found that intact hormone predominated in the circulation but was cleared very rapidly. There was also evidence of fragmentation to polypeptides of molecular weights of 6,000, 4,500 and 2,500. Whether these fragments are biologically active or represent catabolism of the hormone will be the subject of these investigations. We have recently modified the iodination procedure to label the histidine residues of the hormone molecule. Further studies with this more uniformly labeled tyrosine-histidine hormone will facilitate the detection of the smaller amino terminal fragments in the circulation and organs of distribution in a way previously not possible.